Human and rodent transspecies carcinogens (trans-species carcinogens) often demonstrate similar organotropic patterns of neoplasia and loss of heterozygosity (LOH. Recently, we have observed significant chromosome 11 LOH in N5 C57BL/6:129Sv heterozygous p53 mice using simple sequence length polymorphic loci. Primers specific for known SSLP loci revealed amplicons consistent with the two strains, C57BL/6 and 129Sv, in the line. Heterozygosity was unexpected because the mice were reported to be on a C57BL/6-Trp53 (N5) background. We hypothesize that carcinogen induced DNA damage in the p53 haploinsufficient mouse results in illegitimate mitotic recombination during repair and genomic instability leading to neoplasia. By exploiting the observed heterozygosity on chromosome 11 in the 5th backcross generation, we learned that LOH was not restricted to theTrp53 locus. A complete copy of chromosome 11 was lost during exposure to phenolphthalein and lymphomagenesis. The investigation confirmed an aneugenic mechanism of action for phenolphthalein and revealed allelotypes (germline pattern of SSLP loci) that were not consistent with the reported p53 (+/-) C57BL/6 (N5) produced at Taconic by breeding N4 generation p53 nullizygous males to inbred C57BL/6 wildtype females. Chromosome 11 loss also occurred in benzene and p-cresidine induced p53 (+/-) mouse sarcomas (oral, intubation) and thymic lymphomas (inhalation, whole animal) and bladder tumors (dietary). Allelotype data from the benzene and p-cresidine studies are, like those of the phenolphthalein study; inconsistent with the breeding protocol reported by Taconic. The results establish microsatellite (SSLP loci) mapping as a useful tool for determination of LOH in carcinogenesis studies using p53 haploinsufficient mice, e.g. (C57BL/6 x 129Sv) or (C57BL/6 x C3H) F1. In summary, we have shown that in independent studies that there is sufficient heterozygosity on chromosome 11 in the heterozygous p53 deficient (+/-) N5 generation mouse to use microsatellite markers at 5 cM intervals to demonstrate whole or partial chromosome loss through non-disjunction and homologous recombination. Most striking and novel was the observation of an unexpected pattern of germline recombinants (C57BL/6 N4 males crossed to wildtype C57BL/6Tac females). We aim to investigate rates of homologous recombination and determine loci specific positive and negative interference with recombination on chromosome 11 under exposure to environmental carcinogens inducing genomic instability. Specifically, this would enhance our scientific understanding of how this genetically altered mouse model responds when exposed to environmental carcinogens. Using this model, we will determine meiotic (parental and progeny germline) and mitotic recombinant genotype patterns (established in normal somatic tissues of progeny during embryogenesis as well as cancers that arise sporadically with different and unique recombinant genotypes). With microsatellite mapping, we will be able to fine map chromosome 11 sites and rates of homologous recombination and the effect on genomic instability.